Maxillofac Plast Reconstr Surg.  2014 May;36(3):85-93.

Metastasis via Peritumoral Lymphatic Dilation in Oral Squamous Cell Carcinoma

• Kim HS
• Park YW

Abstract

PURPOSE
Nodal metastasis is the main prognostic factor in the patients with oral squamous cell carcinoma (OSCC). We investigated the association between tumor-associated lymphatics and OSCC characteristics.
METHODS
Thirty-four specimens were used for the immunohistochemical staining with the antibody for vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, phosphorylated VEGFR-3, D2-40, and matrix metallproteinases (MMPs). We observed the distribution of the lymphangiogenic factors and quantified the degree of expression. We determined lymphatic vessel density (LVD) and lymphatic vessel dilatation with D2-40 immunostaining. We assessed the association of LVD or lymphatic vessel dilatation with tumor progression or tumor differentiation.
RESULTS
OSCC cells expressed lymphangiogenic ligands. Lymphangiogenic receptor, VEGFR-3, was expressed and activated in some tumor cells as well as in tumor-associated endothelial cells. LVD was not associated with tumor size or nodal status, but lymphatic vessel dilatation was higher in tumors with nodal metastasis, and also higher in poorly differentiated tumors. In stromal area of OSCC, MMP-1 and MMP-10 were up-regulated and the basement membrane of tumor-associated endothelial cells was destroyed by these collagenases.
CONCLUSION
In the primary tumors with nodal metastasis, especially in poorly differentiated OSCC, tumor cells invaded the dilated lymphatic vessels via ruptured sites. MMP-1 and MMP-10 are important in the lysis of the glycocalyx inside the tumor-associated lymphatic endothelial cells.

Keyword

Oral squamous cell carcinoma; Lymphangiogenic factor; Nodal metastasis; Lymphatic vessel density; Lymphatic vessel dilation

MeSH Terms

Basement Membrane
Carcinoma, Squamous Cell*
Collagenases
Dilatation
Endothelial Cells
Glycocalyx
Humans
Ligands
Lymphatic Vessels
Neoplasm Metastasis*
Receptors, Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor D
Vascular Endothelial Growth Factor Receptor-3
Collagenases
Ligands
Receptors, Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor D
Vascular Endothelial Growth Factor Receptor-3